The capacity of lung to remove and metabolize a variety of bioactive substances from pulmonary vascular space has received considerable attention in recent years because of the potential significance of this process in regulating circulating levels of the substances involved. The following studies are proposed with a view to elucidating the nature of this important process of lung: 1) Using intact lung as well as isolated pulmonary endothelial cells examine uptake and metabolism of several clinically important drugs which are structurally related to norepinephrine. 2) Examine the effects of tricyclic antidepressant drugs and related compound on pulmonary deamination of several biogenic monoamines. Method to be used in this study include: 1) Preparation of lung, perfused in vitro, will be used to measure the rate and extend of uptake and metabolism in the intact lung. 2) Preparations of pulmonary endothelial cells and cellulose acetate. 3) Purification of the different forms of pulmonary monoamine oxidase (MAO) to examine the nature of the interaction between tricyclic antidepressant drugs and MAO. It is hoped that this study designed to examine the pulmonary uptake and metabolism process from three levels (intact lung, isolated endothelial cells, subcellular components) will facilitate the understanding of the overall mechanism of this potentially important function of lung.